PROJECT SUMMARY There has been enormous growth in the past few years in our understanding of pathogenic mechanisms in autoimmunity, and a new recognition of the similarities and important distinctions between different autoimmune diseases. Examples of rapidly moving areas of research in autoimmunity are the identification and characterization of new subsets of pathogenic T and B cells that secrete unique inflammatory mediators and novel insights into the interface between genetic susceptibility, environmental stress, and the microbiome and metabolome. These findings have emerged largely from the work of basic scientists, and this FASEB summer conference on Autoimmunity has historically focused on discussion of new findings in basic research in autoimmunity. However, we believe that it is crucial for basic scientists to establish and maintain connections to scientists who are working to translate mechanisms into therapeutic targets. For example, the unexpected efficacy of therapeutic B cell depletion in some autoimmune diseases has prompted intense investigation by basic scientists into the role of B cells in pathogenic pathways. In a like manner, the understanding of the role of the microbiome influencing immune regulation has led to the discussion and development of potentially novel therapeutic strategies for other illnesses, such as inflammatory bowel disease and rheumatoid arthritis. Basic information on metabolism in regulatory and effector T cells has spurred interest in the drive toward metabolic manipulations as therapeutic strategies, not only in cancer, but also in autoimmunity. Notably one of the major complications of cancer immunotherapy with checkpoint inhibitors is the development of a wide- range of autoimmune complications. Therefore, while maintaining a focus on cutting edge basic research in autoimmunity, we will continue to have as speakers translational scientists that focus upon mechanisms of tissue injury in human autoimmune diseases, and that will discuss new strategies for treating autoimmune diseases and current data on the successes and failures of manipulating the immune system in autoimmune humans and cancer patients. We expect that emphasis on therapeutic treatment of autoimmune disease will attract both basic and industry scientists and will stimulate strong interest among both junior and established investigators. The size and setting of this meeting are ideal to promote the open exchange of data and cross- fertilization of ideas that will stimulate new hypotheses and directions in autoimmunity research.